Psychedelics' Interaction With Psych Meds: More Questions Than Answers

Megan Brooks

March 28, 2022

Psychedelics, including psilocybin and MDMA, are promising for a variety of psychiatric disorders, but there are few data showing how these drugs interact with traditional psychiatric medications, new research shows.

Dr Aryan Sarparast

"Despite prolific psychedelic research and public interest, I was surprised to see little clinical research on how psilocybin and common psychiatric treatments interact," study investigator Aryan Sarparast, MD, Department of Psychiatry, Oregon Health and Science University, Portland, told Medscape Medical News.

The review was published online March 7 in Psychopharmacology.

Need for RCTs

The US Food and Drug Administration recently granted breakthrough therapy designation to psilocybin-assisted psychotherapy for major depression and treatment-resistant depression and to MDMA-assisted psychotherapy for posttraumatic stress disorder.

The investigators assessed the volume of available research on interactions between psychedelics and traditional psychiatric medications, such as antidepressants.

They found 40 studies dating back to 1958, including 26 randomized controlled trials, 11 case reports, and three epidemiologic studies.

Only one randomized clinical trial evaluated the interaction between psilocybin and the most common psychiatric treatment, selective serotonin reuptake inhibitors (SSRIs), said Sarparast.

However, this study is "reassuring and overlaps with our hypothesis that there is a low risk of psilocybin and most psychiatric drugs causing harm when combined," he noted.

Yet all of the clinical trials exclusively included young healthy adults, who were often recruited from university campuses. "We don't have data on what happens when a depressed person on an SSRI takes psilocybin," said Sarparast.

He added that he is concerned that the lack of evidence on drug-drug interactions will lead some providers to require patients to be tapered off existing traditional psychiatric medications before initiation of psilocybin therapy.

This may force vulnerable patients to choose between their existing therapy and psilocybin.

In addition, patients who opt for the "DIY method" of tapering risk mental health relapse and medication withdrawal effects. "That's a very, very tough place to be," Sarparast said.

Ideally, said Sarparast, he would like to see a study in which depressed patients who have been receiving long-term antidepressant treatment are randomly assigned to received low, medium, and high doses of psilocybin. "This would clarify a lot of question marks," he noted.

Evidence Gap

Commenting for Medscape Medical News, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, said, "The point in this article is very well taken. Indeed, more research is needed" on potential interactions between psychedelics and traditional psychiatric medications.

"Before we embark on completing research and development for psychedelics ― or, for that matter, any psychoactive substance ― we should endeavor to identify what the potential safety and toxicity concerns are when they are co-prescribed with other prescribed medications, over-the-counter medications, and other substances (eg, marijuana) that people take," McIntyre said.

A case in point ― a recent study conducted by McIntyre and colleagues revealed "significant drug-drug interactions with cannabis, which never receives that much attention," McIntyre said.

Also weighing in for Medscape Medical News, Albert Garcia-Romeu, PhD, assistant professor of psychiatry and behavioral sciences, Johns Hopkins University School of Medicine, Baltimore, confirmed that there is "an evidence gap" on psilocybin's and other psychedelic drugs' interactions with other medications.

"This has not been formally studied for a number of reasons, but mainly because psilocybin has primarily been considered a drug of abuse. Psilocybin has only recently started to be looked at as a potential medication, and as such, research on drug-drug interactions is still limited, but growing," Garcia-Romeu told Medscape Medical News.

He noted that studies are underway to better understand potential interactions between psilocybin and other medications.

"This will allow us to better understand how psilocybin should be used medically and what types of interactions could occur with other drugs or medications," Garcia-Romeu added.

The study had no specific funding. Sarparast, McIntyre, and Garcia-Romeu report no relevant financial relationships.

Psychopharmacol. Published online March 7, 2022. Abstract

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